Fujimoto S, Ogawa M
Division of Clinical Chemotherapy, Japanese Foundation for Cancer Research, Tokyo.
J Pharmacobiodyn. 1987 Jul;10(7):341-5. doi: 10.1248/bpb1978.10.341.
In order to further evaluate the antitumor activity of 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077), the therapeutic ratios (a ratio of the optimal dose versus the dose showing 25% increase in life span) of TA-077 were examined using two L1210 leukemia systems and the results were compared with those of twenty-six antitumor agents for reference. In the i.p.-i.p. system, in which the tumor cells were inoculated intraperitoneally (i.p.) and the drugs were also administered i.p., TA-077 administered daily for five consecutive days showed a therapeutic ratio of 40.6, which was the third highest of all drugs tested. However, in the i.v.-i.v. system, in which the tumor cells were inoculated intravenously (i.v.) and the drugs were also administered i.v., TA-077 given on the same schedule showed a ratio of 13.7, which was the highest of all the drugs examined. The results of the present study also indicated that L1210 leukemia cells were highly sensitive to nitrosourea derivatives. Therefore, this should be taken into consideration for screening of candidates for new antitumor agents.
为了进一步评估1-(2-氯乙基)-3-异丁基-3-(β-麦芽糖基)-1-亚硝基脲(TA-077)的抗肿瘤活性，使用两种L1210白血病模型检测了TA-077的治疗指数(最佳剂量与使寿命延长25%的剂量之比)，并将结果与26种抗肿瘤药物进行比较以供参考。在腹腔内接种肿瘤细胞并腹腔内给药的腹腔-腹腔模型中，连续5天每日给予TA-077，其治疗指数为40.6，在所有受试药物中排第三高。然而，在静脉接种肿瘤细胞并静脉给药的静脉-静脉模型中，按相同给药方案给予TA-077，其治疗指数为13.7，在所有受试药物中最高。本研究结果还表明，L1210白血病细胞对亚硝基脲衍生物高度敏感。因此，在筛选新型抗肿瘤药物候选物时应考虑这一点。
